Doctors seek ways to protect memory from normal wear-and-tear

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WASHINGTON — When aging hampers memory, some people's brains compensate to stay sharp. Now scientists want to know how those brains make do — in hopes of developing treatments to help everyone else keep up.

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This is not Alzheimer's disease, but the wear-and-tear of so-called normal aging. New research is making clear that memory and other brain functions decline to varying degrees even in otherwise healthy people as they age, as anyone who habitually loses car keys probably suspected.

The question is how to gird our brains against time's ravages, a question becoming critical as the population grays. If you're 65 today, odds are you'll live to 83. But improving health care means people in their 50s today may live another 40 years.

"I don't think we've recognized, as scientists or a society, (that) this is the front-and-center public health issue we face as a nation," Dr. Denise Park, director of the University of Illinois' Center for Healthy Minds, told fellow brain specialists assembled by the government last week.

"We need to understand how to defer normal cognitive aging ... the way we've invested in fighting heart disease and cancer."

Forging new pathwaysThere are intriguing clues, gleaned from discoveries that some seniors' brains literally work around aging's damage, forging new pathways when old ones disintegrate.

"It's not just fanciful or pie-in-the-sky" to try harnessing that ability, said Dr. Richard Hodes, director of the National Institute on Aging, which organized last week's meeting to seek advice on the most promising research.

High on the list: Simple physical exercise. It seems to do the brain as much good as the body.

Other options aren't as well-studied, but range from brain-training games to medications that may keep brain networks better connected. In fact, an old blood-pressure pill named guanfacine improves memory in old rats and monkeys by doing just that — but it hasn't yet been tested in older people with memory problems.

What's normal aging and what signals impending Alzheimer's? That is a big question for elders worried about periodic memory lapses. Science can't yet tell for sure, but there seem to be distinct differences.

Bushy brainsConsider: A healthy brain is a bushy one. Branch-like tentacles extend from the ends of the brain's cells, enabling them to communicate with each other. The more you learn, the more those connections form.

Alzheimer's kills neurons, so the cells disappear along with connections their neighbors need.

With normal aging, the cells don't die but their bushes can shrivel to skinny twigs, explained Dr. Carol Barnes of the University of Arizona. Cells that are less connected have a harder time sending messages. You may know someone's name, but not be able to recall it.

Moreover, Alzheimer's seems to first target a different spot in the hippocampus, the brain's memory center, than aging does.

There are two capacities for fighting back:

Some brains withstand a lot of assault before showing symptoms, something called "cognitive reserve." Indeed, striking autopsy studies have found between 20 percent and 40 percent of elders who displayed no confusion actually had brains riddled with Alzheimer's trademark plaques. Presumably, they had such bushy brains that even when some neurons died, enough were left to function.

Compensation is how the brain adapts when old pathways quit functioning, to reroute itself and use alternates. Brain scans show younger people tend to use different neural networks than older people when performing the same task.

'Use-it-or-lose-it'What's the advice for now?

Physical exercise is the best-proven prescription so far, the scientists agreed. Memory improved when 72-year-olds started a walking program three days a week, and sophisticated scans showed their brains' activity patterns started resembling those of younger people,

Then there's the "use-it-or-lose-it" theory, that people with higher education, more challenging occupations and enriched social lives build more cognitive reserve than couch potatoes.

It's never too late to start building up that reserve, said Columbia University neuroscientist Yaakov Stern. But, "the question is how. What is the recipe?"

Everything from doing crossword puzzles to various computer-based brain-training programs has been touted, but nothing is yet proven to work. Johns Hopkins University has a major government-funded study under way called the "Experience Corps," where older adults volunteer to tutor school students 15 hours a week, to see if such long-term stimulation maintains the elders' brains.

What about medication? Companies have been reluctant to test side effect-prone drugs in an otherwise healthy aging brain, but scientists cited animal studies suggesting low-dose estrogen and drugs that might mimic or ramp up brain signaling are promising possibilities.

And recall that old blood pressure drug guanfacine? It is now being studied as a potential treatment for children with attention-deficit disorder — and it works in the same brain region, the prefrontal cortex, where elderly brains forge new networks.

"If it works in a 6-year-old, we hope it will work in the elderly," said Yale University neurobiologist Amy Arnsten.

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